This invention concerns a novel dibenzothiazepine compound useful for its antidopaminergic activity, for example, as an antipsychotic or neuroleptic.
Previous attempts at finding compounds useful in a variety of applications have included U.S. Pat. No. 3,539,573 to Schmutz et al. which discloses selected dibenzothiazepines and dibenzodiazepines as being useful for a variety of medical conditions including as neuroleptic-antidepressants, or neuroleptics. U.S. Pat. No. 3,389,139 to Schmutz et al. teaches compounds based on 6-basic substituted morphanthridines as neuroplegics, neuroleptics and analgesics, with selected compounds being useful for treating psychotic conditions. U.S. Pat. No. 4,097,597 to Horrom et al. discloses dibenzodiazepine derivatives useful as antischizophrenics.
A compound of the following formula I ##STR1## in which X may be as shown in formula Ia ##STR2## and R may be (CH.sub.2 CH.sub.2 O ).sub.2 H, has been Anonymously disclosed in Res. Discl. (1980), 192: 158-9.
Compounds used as antipsychotics and neuroleptics have, however, been plagued by the problems of undesired side effects. Such side effects include acute dyskinesias, acute dystonias, motor restlessness, pseudo-Parkinsonism and tardive dyskinesias (TD). Acute syndromes usually have an early onset, for example, 1 to 5 days for acute dystonias and dyskinesias, and may include torsion spasms, muscle spasms and dystonia of the face, neck or back with protrusion of the tongue and tonic spasms of the limbs (dyskinesia). Tardive dyskinesia has a time of maximal risk after months or years of treatment. TD's comprise oral-facial dyskinesia, lingual-facial-buc-cal-cervical dystonias sometimes with involvement of the trunk and extremities. TD's also include repetitive stereotypical movements of the face, tongue and limb such as sucking and smacking of the lips, lateral jaw movements and protrusions of the tongue. When the antipsychotic drug treatment is stopped the symptoms continue, often for months or years. These involuntary movements constitute the most undesirable side effect of antipsychotic drug treatment; for example, the percentage of patients that develop TD has been variously reported to be as high as 20 percent. Thus, there still remains a need for compounds which exhibit antidopaminergic activity without the side effects heretofore experienced with previous compounds.